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1.
Oral Oncol ; 152: 106755, 2024 May.
Article in English | MEDLINE | ID: mdl-38547780

ABSTRACT

OBJECT: Previous studies suggest BRAFV600E mutation is a marker for poor prognosis in papillary thyroid cancer, however, its ability to further risk stratify papillary thyroid microcarcinoma (PTMC) remains controversial. We aimed to explore the association between BRAFV600E mutation and the clinicopathological features and recurrence in Chinese PTMC patients. METHODS: We retrospectively reviewed 2094 PTMC patients who underwent surgery and had a valid BRAFV600E mutation test result. Among them, 1292 patients had complete follow-up data. The mutation incidence was determined. Moreover, the clinicopathological characteristics, disease-free survival (DFS), and response to therapy distribution were compared between the mutation and non-mutation groups. RESULTS: BRAFV600E mutation was observed in 90.6 % of all patients and 89.2 % of patients with complete follow-up data. No significant difference was observed in lymph node metastases (LNM) number categories between the mutation and non-mutation groups among all patients (P = 0.329) and 1292 patients (P = 0.408). Neither the 3-year DFS (97.9 % vs. 98.0 %, P = 0.832) nor the response to therapy distribution (P > 0.05) indicated a significant difference between the mutation and non-mutation groups. The 3-year DFS differs among patients having different LNM number categories (99.8 % vs. 98.5 % vs. 77.3 %, P < 0.001). Multivariate analysis revealed that high-volume (over 5) LNM (Total thyroidectomy (TT): OR = 4.000, 95 % CI 2.390-6.694, P < 0.001; Unilateral thyroidectomy (UT): OR = 4.183, 95 % CI 1.565-11.190, P = 0.004), rather than BRAFV600E mutation (P > 0.05), was an independent risk factor of response to therapy. CONCLUSIONS: Our results suggested that BRAFV600E mutation could not accurately predict LNM or the recurrence of Chinese PTMC patients. Moreover, high-volume LNM is significantly associated with PTMC prognosis.


Subject(s)
Mutation , Proto-Oncogene Proteins B-raf , Thyroid Neoplasms , Humans , Female , Male , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Neoplasms/therapy , Middle Aged , Proto-Oncogene Proteins B-raf/genetics , Adult , Retrospective Studies , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Aged , Neoplasm Recurrence, Local/genetics , Prognosis , Young Adult
2.
Nat Prod Bioprospect ; 14(1): 17, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38407685

ABSTRACT

Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1ß production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

3.
Curr Med Sci ; 44(1): 232-240, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38393530

ABSTRACT

OBJECTIVE: Secoemestrin C (SC), an epitetrathiodioxopiperazine isolated from Aspergillus nidulans, has been previously reported to have immunomodulatory and hepatoprotective effects against acute autoimmune hepatitis. However, the effect of SC on regulating the inflammation and its underlying mechanisms in the pathogenesis of psoriasis remain unclear. This study aimed to evaluate the effects of SC on inflammatory dermatosis both in vitro and in vivo. METHODS: In vitro, HaCaT cells were induced with tumor necrosis factor-alpha (TNF-α, 10 ng/mL) to establish an inflammatory injury model, and the expression of nuclear transcription factor-κB (NF-κB) pathway components was measured using qRT-PCR and Western blotting. An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like skin inflammation was used to evaluate the effectiveness of SC in alleviating psoriasis. RESULTS: SC significantly blocked the activation of NF-κB signaling in TNF-α-stimulated HaCaT cells. In addition, systemic and local administration of SC improved psoriatic dermatitis in the IMQ-induced mouse model. SC reduced skin scale and significantly inhibited the secretion of inflammatory factors in skin lesions. CONCLUSION: The protective effect of SC against psoriatic-associated inflammation reveals its potential therapeutic value for treating psoriasis.


Subject(s)
Dermatitis , Psoriasis , Signal Transduction , Animals , Mice , Dermatitis/complications , Dermatitis/drug therapy , Imiquimod/adverse effects , Inflammation/drug therapy , Inflammation/chemically induced , NF-kappa B/metabolism , Psoriasis/chemically induced , Psoriasis/drug therapy , Psoriasis/genetics , Tumor Necrosis Factor-alpha/metabolism
4.
Radiother Oncol ; 190: 110023, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37995850

ABSTRACT

OBJECTIVES: Examine the significance of contouring the brachial plexus (BP) for toxicity estimation and select metrics for predicting radiation-induced brachial plexopathy (RIBP) after stereotactic body radiotherapy. MATERIALS AND METHODS: Patients with planning target volume (PTV) ≤ 2 cm from the BP were eligible. The BP was contoured primarily according to the RTOG 1106 atlas, while subclavian-axillary veins (SAV) were contoured according to RTOG 0236. Apical PTVs were classified as anterior (PTV-A) or posterior (PTV-B) PTVs. Variables predicting grade 2 or higher RIBP (RIBP2) were selected through least absolute shrinkage and selection operator regression and logistic regression. RESULTS: Among 137 patients with 140 BPs (median follow-up, 32.1 months), 11 experienced RIBP2. For patients with RIBP2, the maximum physical dose to the BP (BP-Dmax) was 46.5 Gy (median; range, 35.7 to 60.7 Gy). Of these patients, 54.5 % (6/11) satisfied the RTOG limits when using SAV delineation; among them, 83.3 % (5/6) had PTV-B. For patients with PTV-B, the maximum physical dose to SAV (SAV-Dmax) was 11.2 Gy (median) lower than BP-Dmax. Maximum and 0.3 cc biologically effective doses to the BP based on the linear-quadratic-linear model (BP-BEDmax LQL and BP-BED0.3cc LQL, α/ß = 3) were selected as predictive variables with thresholds of 118 and 73 Gy, respectively. CONCLUSION: Contouring SAV may significantly underestimate the RIBP2 risk in dosimetry, especially for patients with PTV-B. BP contouring indicated BP-BED0.3cc LQL and BP-BEDmax LQL as potential predictors of RIBP2.


Subject(s)
Brachial Plexus Neuropathies , Radiation Injuries , Radiosurgery , Humans , Radiosurgery/adverse effects , Radiotherapy Dosage , Organs at Risk , Brachial Plexus Neuropathies/etiology , Radiotherapy Planning, Computer-Assisted
5.
Clin Exp Immunol ; 215(3): 261-267, 2024 02 19.
Article in English | MEDLINE | ID: mdl-38066563

ABSTRACT

BACKGROUND: Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency. X-linked (XL) CGD caused by gene defects of CYBB is the most prevalent type of CGD. OBJECTIVE: We aim to understand the clinical and molecule features of XL-CGD secondary to skewed X-chromosome inactivation (XCI) in female. METHODS: We retrospectively reviewed the medical records of a female patient diagnosed with XL-CGD. Flow cytometry was used to detect the respiratory burst function. After restriction enzyme digestion of DNA, XCI was calculated by detecting fluorescent PCR products with capillary electrophoresis. The previously published female XL-CGD cases secondary to skewed XCI was summarized. RESULTS: Clinical data were available for 15 female subjects. The median age of diagnosis was 16 years. Consistent with XL-CGD in males, infection was the most frequent manifestation in the female patients. Catalase-positive pathogens including Serratia marcescens and Staphylococcus aureus infections were the most common pathogens. Autoimmune/autoinflammation manifestations were observed in five patients. Dihydrorhodamine (DHR) assay showed that median %DHR+ values were 6.5% and the values varying with age were observed in 2 patients. All patients had a skewing XCI and there was no consistency between the daughter and carrier mother. Anti-infective treatment was effective in majority and there was no mortality reported in XL-CGD female patients to date. CONCLUSION: XL-CGD should not be neglected in female patients manifested as CGD phenotype and it is necessary to make periodic clinical evaluation of CGD female carriers as the neutrophil oxidative function may decline with aging and increase the risk for infection.


Subject(s)
Granulomatous Disease, Chronic , Male , Humans , Female , Adolescent , Granulomatous Disease, Chronic/genetics , Granulomatous Disease, Chronic/diagnosis , Retrospective Studies , X Chromosome Inactivation , Neutrophils , Chromosomes
6.
Front Immunol ; 14: 1267933, 2023.
Article in English | MEDLINE | ID: mdl-37809096

ABSTRACT

Cryopyrin-associated periodic syndrome (CAPS) comprises a group of disorders characterized by recurrent bouts of systemic inflammation related to overactivation of inflammasome. So far, neither large cases of the correlation between genotype and phenotype nor treatment strategies have been clearly stated in China. Here, we studied the clinical and genetic characteristics and their correlation from 30 CAPS patients in China. We identified the pathogenesis for novel mutations by activating NLRP3 inflammasome for peripheral cells with ATP plus LPS, compared characteristics with other case series, and analyzed treatment outcomes of these patients. The patients harbored 19 substitutions in NLRP3, and 8 of them were novel mutations. Among these novel mutations, percentages of severe musculoskeletal, ophthalmologic, and neurological symptoms were higher compared with other case serials. The correlation of phenotypes and their variants seemed different in our cases, such as T350M, S333G/I/R, and F311V (somatic mosaicism). Ten patients received Canakinumab treatment, which proved effective at alleviating musculoskeletal, neurological, auditory, visual manifestations, fever, and rash for 10-20 months follow-up. Patients treated with prednisolone or prednisolone plus thalidomide or methotrexate, tocilizumab, TNF inhibiting agents, and sirolimus achieved only partial remission. Importantly, we firstly identified somatic mosaicism mutation of F311V, which was severe. Our study extended the spectrum of genotype and phenotype and characteristics of their correlations and provided detailed responses to different treatment strategies. These data provide guidance for future diagnosis and management for CAPS.


Subject(s)
Cryopyrin-Associated Periodic Syndromes , Child , Humans , Cryopyrin-Associated Periodic Syndromes/drug therapy , Cryopyrin-Associated Periodic Syndromes/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Cohort Studies , Inflammasomes , China , Prednisolone/therapeutic use
7.
Nanoscale ; 15(36): 14886-14895, 2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37650354

ABSTRACT

Plasmonic hybrids are regarded as promising candidates for water purification due to their structure-dependent photocatalysis and photothermal performance. It remains a challenge to develop materials that possess these two characteristics for efficient water purification. Herein, plasmonic Ti3C2Tx/Bi2S3 two-dimensional (2D)/2D hybrids were prepared for efficient solar-driven water purification via the combination of photothermal conversion and photocatalysis. Benefitting from broad light absorption, large 2D/2D interfaces, and efficient charge transfer, the binary hybrids showed high-efficiency photothermal conversion and photothermal-assisted photocatalytic activity. By depositing these 2D/2D hybrids on a hydrophilic and porous cotton piece, the Ti3C2Tx/Bi2S3 membrane displayed a high water evaporation rate and solar-to-vapor efficiency under one-sun irradiation. The solar-driven evaporation of seawater, heavy metal ion solution, and dye solution jointly indicated that the plasmonic membrane shows great potential for drinkable water generation and industrial wastewater treatment. Most importantly, the synergistic effect of photothermal evaporation and photocatalysis of the Ti3C2Tx/Bi2S3 membrane on water purification was demonstrated. The polluted water can not only be treated by evaporation, but also be degraded via photocatalysis under solar light irradiation. This work provides new insight into designing functional materials for water purification based on the combination of photothermal conversion and photocatalysis.

8.
Molecules ; 28(13)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37446777

ABSTRACT

The effective control over the vesicle formation pathways is vital for tuning its function. Recently, a liquid-liquid phase-separated intermediate (LLPS) is observed before a vesicular structure during the solvent exchange self-assembly of block copolymers. Though the understanding of polymer structures and chemical compositions on the competition between LLPS and micellization has made some progress, little is known about the role of cosolvent on it. In this study, the influence of cosolvent on the vesicle formation pathways is investigated by using dissipative particle dynamics. The results show that the range of water fraction within which the LLPS is favored will be highly dependent on the affinity difference of cosolvent to water and to polymer repeat units. The change of the cosolvent-water interaction and the water fraction impact the distribution of cosolvent in the polymer domain, the miscibility between the components in the system as well as the chain conformations, which finally induce different self-assembly behaviors. Our findings would be helpful for understanding the LLPS and controlling the morphologies of diblock polymers in solutions for further applications.


Subject(s)
Polymers , Water , Solvents/chemistry , Polymers/chemistry , Water/chemistry
9.
World J Pediatr ; 19(7): 687-700, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37154862

ABSTRACT

BACKGROUND: Adenosine deaminase (ADA) is a key enzyme in the purine salvage pathway. Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency. To date, few Chinese cases have been reported. METHODS: We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature. RESULTS: Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive. CONCLUSIONS: This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.


Subject(s)
Intracranial Aneurysm , Severe Combined Immunodeficiency , Humans , Adenosine Deaminase/genetics , Adenosine Deaminase/metabolism , Failure to Thrive , Mutation , Retrospective Studies , RNA Precursors , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/genetics , Silent Mutation , Infant
10.
J Clin Immunol ; 43(6): 1193-1207, 2023 08.
Article in English | MEDLINE | ID: mdl-36947335

ABSTRACT

The dedicator of cytokinesis 2(DOCK2) protein, an atypical guanine nucleotide exchange factor (GEFs), is a member of the DOCKA protein subfamily. DOCK2 protein deficiency is characterized by early-onset lymphopenia, recurrent infections, and lymphocyte dysfunction, which was classified as combined immune deficiency with neutrophil abnormalities as well. The only cure is hematopoietic stem cell transplantation. Here, we report two patients harboring four novel DOCK2 mutations associated with recurrent infections including live attenuated vaccine-related infections. The patient's condition was partially alleviated by symptomatic treatment or intravenous immunoglobulin. We also confirmed defects in thymic T cell output and T cell proliferation, as well as aberrant skewing of T/B cell subset TCR-Vß repertoires. In addition, we noted neutrophil defects, the weakening of actin polymerization, and BCR internalization under TCR/BCR activation. Finally, we found that the DOCK2 protein affected antibody affinity although with normal total serum immunoglobulin. The results reported herein expand the clinical phenotype, the pathogenic DOCK2 mutation database, and the immune characteristics of DOCK2-deficient patients.


Subject(s)
GTPase-Activating Proteins , Immunologic Deficiency Syndromes , Humans , Vaccines, Attenuated , GTPase-Activating Proteins/genetics , Reinfection , Guanine Nucleotide Exchange Factors/genetics , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/therapy , Mutation , Receptors, Antigen, T-Cell/genetics
12.
China Pharmacy ; (12): 2350-2355, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-996391

ABSTRACT

OBJECTIVE To investigate the effect and mechanism of α7 nicotinic acetylcholine receptor (α7nAChR) agonists PNU-282987 on cognitive function in temporal lobe epilepsy (TLE) model rats. METHODS Sixty rats were randomly divided into control group, model group, PNU-282987 group (3 mg/kg) and methyllycaconitine (MLA)+PNU-282987 group (6 mg/kg MLA+3 mg/kg PNU-282987), with 15 rats in each group. Except for control group, the TLE model was established in the other groups. After the model was successfully established, each group was given relevant medicine or normal saline intraperitoneally, once a day, for two consecutive weeks. The epilepsy attack of rats was observed and scored, and the duration of seizures was recorded; the cognitive function of rats was detected; pathological morphology of neurons in CA1 region was observed; the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in the hippocampus were detected; the positive expressions of ionized calcium-binding adapter molecule-1 (IBA-1), α7nAChR, nuclear factor-κB (NF-κB) p65, p-NF-κB p65 in the hippocampus were detected. RESULTS Compared with model group, the score and duration of seizures, the number of IBA-1 positive cells, the levels of TNF- α, IL-6 and IL-1β, the expressions of NF- κB p65 and p-NF- κB p65 protein decreased significantly in the hippocampus (P<0.05); the escape latency time was shortened significantly (P<0.05), the time spent in the original platform quadrant and times of crossing the platform increased significantly (P<0.05); neuronal damage in the CA1 region of the hippocampus was significantly reduced; the expression of α7nAChR protein increased significantly in hippocampus (P<0.05). Compared with PNU-282987 group, the above indexes of rats in MLA+PNU-282987 group were reversed significantly (P<0.05). CONCLUSIONS PNU-282987 could improve cognitive dysfunction in TLE model rats, and its mechanism may be associated with inhibiting microglia-mediated inflammatory response through α7nAChR/NF- κB signaling pathway, thus reducing hippocampal neuronal damage.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-995615

ABSTRACT

Objective:To observe the clinical and fundus imaging features of acute macular neuroretinopathy (AMN) associated with COVID-19.Methods:A retrospective case study. A total of 32 eyes of 18 patients diagnosed of AMN associated with COVID-19 at Chengdu Aidi Eye Hospital from December 2022 to February 2023 were included. All patients had a history of fever 1 to 5 days prior to ocular onset and tested positive for SARS CoV-2 antigen. All patients were examined by best-corrected visual acuity (BCVA), color fundus photography, scanning laser ophthalmoscope (SLO), infrared fundus photography (IR), and optical coherence tomography (OCT); OCT angiography, visual field and multifocal electroretinogram (mf-ERG) were performed in 6 patients (11 eyes), 3 patients (6 eyes) and 1 patient (2 eyes), respectively. Follow-up time was 8-10 weeks. The clinical and fundus imaging features were observed and analyzed.Results:There were 6 males (12 eyes) and 12 females (20 eyes), aged from 15 to 36 years, with the mean age of (28.00±5.86) years. Fourteen patients were bilateral and 4 patients were unilateral. The time from the onset of eye symptoms to seeing a doctor was ranged from 1 day to 8 weeks. Among them, 6 patients (10 eyes) visited the doctor within 3 days of onset, while 12 patients (22 eyes) visited the doctor after 3 days of onset. The BCVA was 0.80±0.29. Fundus color photography and SLO examination showed that only 2 patients (4 eyes) showed sheet or petal-like dark red lesions in the macular area, and no obvious abnormal changes were observed in other patients. No obvious abnormalities were found in AF examination of all patients. IR examination showed no significant abnormality in 6 cases which came to hospital within 3 days after the onset, but irregular hyporeflective dark shadow lesions in the macular region of patients with more than 3-day course of disease was observed. OCT examinations of all eyes showed hyperreflective band or patchy lesion on the outer plexiform layer (OPL) and outer nuclear layer (ONL) and affect the ellipsoid zone (EZ) and interdigitation zone (IZ). In 11 eyes of 6 patients undergoing OCTA examination, the blood flow density of the choroidal capillary layer in the focal area decreased. In 6 eyes of 3 patients who underwent visual field examination, the physiologic scotoma was slightly enlarged. One patient (2 eyes) receiving mf-ERG showed a concave reduction in macular center amplitude. The hyperreflective band lesion on OPL and ONL disappear rapidly within 2 weeks, while the continuity of EZ recovered slowly, and the disruption of IZ kept existing for more than 10 weeks.Conclusions:Most AMN associated with COVID-19 are young women; IR showed irregular weak reflex in the lesion area. OCT showed strong OPL and ONL reflection. OCTA was characterized by decreased blood flow density in the choroidal capillary layer of the focal area.

14.
Chinese Journal of Neurology ; (12): 220-226, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-994822

ABSTRACT

With rapid global growth of the older population, it has been increasingly important for screening, early diagnosis, treatment and daily monitoring of cognitive function in the elderly population. Given the limited effects of pharmacological treatments, cognitive rehabilitation has the potential to improve meaningful outcomes for older people and thus comes into sight. Traditional cognitive assessment and rehabilitation require face-to-face interview, while patients with cognitive impairment are mostly elderly with difficulties in access to medical care, usually needed to be accompanied by caregivers and having other co-morbidities with limited mobility. This contradiction is especially prominent in the context of COVID-19 pandemic, which may even exacerbate cognitive decline of patients. Therefore, remote cognitive assessment and rehabilitation based on information and communication technologies have become new options. This paper introduces the widely used and validated means of remote assessment and its guiding use in cognitive rehabilitation, which can be implemented through the Internet, applications, video and telephone. The advantages of being fast, convenient and geographically agnostic lead to a wider use in large community and safeguard the health of patients with cognitive impairment.

15.
Chinese Journal of Hematology ; (12): 380-387, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-984633

ABSTRACT

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.


Subject(s)
Female , Humans , Male , Aged , Middle Aged , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Prognosis , Lymphoma, B-Cell , Immunohistochemistry , Immunoglobulin Heavy Chains/therapeutic use
16.
IEEE Trans Biomed Circuits Syst ; 16(6): 1153-1165, 2022 12.
Article in English | MEDLINE | ID: mdl-36441889

ABSTRACT

In this study, a 0.8-V- Vin 200-mA- Io capless low-dropout voltage regulator (LDO) is developed for a wireless respiration monitoring system. The biaxially driven power transistor (BDP) technique is proposed in the LDO, with a current driven stimulation on the bulk and a voltage on the gate terminal. With the BDP technique, an adaptively biased current-driven loop (ABCL) is designed which can reduce the high threshold voltage of power transistor, thus presenting lower input voltage and reduced power consumption. Moreover, this loop can provide an improved dynamic response due to its increased discharging current. Based on an error amplifier with enhanced DC gain and gain bandwidth, the capless LDO achieves superior power supply rejection (PSR) and stability without a complex frequency compensation mechanism. The proposed LDO is fabricated in the SMIC 180 nm process with a chip area of 0.046 mm 2. Measurement results indicate that this LDO can obtain a 200-mA load current range and greater than -66 dB PSR up to 1 kHz at a supply voltage as low as 0.8 V.


Subject(s)
Electric Power Supplies , Electrocardiography , Equipment Design , Amplifiers, Electronic
17.
Adv Sci (Weinh) ; 9(32): e2203460, 2022 11.
Article in English | MEDLINE | ID: mdl-36089657

ABSTRACT

Respiration signals reflect many underlying health conditions, including cardiopulmonary functions, autonomic disorders and respiratory distress, therefore continuous measurement of respiration is needed in various cases. Unfortunately, there is still a lack of effective portable electronic devices that meet the demands for medical and daily respiration monitoring. This work showcases a soft, wireless, and non-invasive device for quantitative and real-time evaluation of human respiration. This device simultaneously captures respiration and temperature signatures using customized capacitive and resistive sensors, encapsulated by a breathable layer, and does not limit the user's daily life. Further a machine learning-based respiration classification algorithm with a set of carefully studied features as inputs is proposed and it is deployed into mobile clients. The body status of users, such as being quiet, active and coughing, can be accurately recognized by the algorithm and displayed on clients. Moreover, multiple devices can be linked to a server network to monitor a group of users and provide each user with the statistical duration of physiological activities, coughing alerts, and body health advice. With these devices, individual and group respiratory health status can be quantitatively collected, analyzed, and stored for daily physiological signal detections as well as medical assistance.


Subject(s)
Wearable Electronic Devices , Humans , Monitoring, Physiologic , Respiration , Computers , Machine Learning
18.
Sensors (Basel) ; 22(9)2022 Apr 28.
Article in English | MEDLINE | ID: mdl-35591086

ABSTRACT

A clock-induced-spurs detector, composed of a programmable low-pass filter (LPF), energy detector and spur detection algorithm, is presented and applied to a four-channel 1 gigabit-samples-per-second (GSPS) direct digital frequency synthesizer (DDS). The proposed detector realizes the detection of spurs based on energy-detection, and the spur detection algorithm is adopted to automatically extract the amplitude and phase of clock-induced spurs, generated by the intermodulation of harmonic spurs and multiple clocks. Finally, the extracted features are sent to auxiliary DDS to decrease the target spur, following which the detector can be turned off to save power. Additionally, the detected characteristics under different output conditions can be read out through the interface for rapid frequency switching. The proposed detector integrated into a DDS is fabricated with a 65 nm complementary metal oxide semiconductor (CMOS) process and has an area of 190 µm × 320 µm. The measured power consumption is roughly 38 mW, consuming 6% that of a single-channel DDS. The test results show that the spurious-free dynamic range (SFDR) of this DDS can be successfully enhanced from -43.1 dBc to roughly -59.9 dBc without any off-chip instruments. This effectively proves that the detection accuracy of this detector can reach around -81 dBm.

19.
Eur J Pediatr ; 181(2): 529-538, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34405301

ABSTRACT

T cell receptor excision circles (TRECs) are small circularized DNA elements produced during rearrangement of T cell receptor (TCR) genes. Because TRECs are fairly stable, do not replicate during mitosis, and are not diluted during division of naïve T cells (Dion et al. [1]), they are suitable for assessing the number of newly formed T cells (Ping and Denise [2]). In this study, we detected TRECs in 521 healthy Chinese children aged 0-18 years in different clinical settings. The TRECs decrease with aging and show lower levels in preterm and low birth weight (BW) babies compared to those in full-term infants, while the preterm babies can also show comparable levels of TRECs when they have a gestation age (GA)-matched BW. We found a strong correlation between TRECs and peripheral CD4 naïve T cell numbers, which was age-related. We also analyzed the TRECs in different PIDs. Since T cell defects vary in PIDs, TREC levels change inconsistently. For example, in Wiskott-Aldrich syndrome (WAS), combining the level of TREC with lymphocyte subsets can help to distinguish subtypes of disease.Conclusion: We established the reference value range for TRECs by evaluating children below 18 years old in China, which could be used to screen for PIDs during early life. What is Known: • The TREC levels are decreased with age, and there is a positive correlation between TRECs and the numbers of naïve T cells. What is New: • This is the largest study to determine TREC reference levels in healthy Chinese pediatric, we provide solid data showing a correlation between CD4 naïve T cell counts and TREC levels according to age. We point out the GA matched BW is need to be considered during the SCID newborn screening. We are the first group showed that TREC levels can help clinician distinguish different WAS phenotype.


Subject(s)
DNA, Circular , Gene Rearrangement, T-Lymphocyte , Receptors, Antigen, T-Cell , T-Lymphocytes , Adolescent , Age Factors , Asian People , Child , Child, Preschool , China , DNA , Humans , Infant , Infant, Low Birth Weight , Infant, Newborn , Neonatal Screening , Receptors, Antigen, T-Cell/genetics , Sex Factors , Wiskott-Aldrich Syndrome/diagnosis , Wiskott-Aldrich Syndrome/genetics
20.
ACS Omega ; 7(51): 48438-48446, 2022 Dec 27.
Article in English | MEDLINE | ID: mdl-36591166

ABSTRACT

The rational design of Raman substrate materials with prominent electromagnetic enhancement and charge transfer is quite important for surface-enhanced Raman scattering (SERS). Herein, an efficient SERS substrate based on two-dimensional ultrathin Ti3C2T x MXene and rough-surfaced Au nanotriangles (NTs) was successfully prepared for efficient detection of organic molecules due to the synthetic effect of an optimized electromagnetic field and charge transfer. Uniform Au NTs with tunable surface roughness were controllably prepared by selectively depositing of Au on the smooth Au NTs. Due to the large surface area, tunable plasmon resonance, and abundant hotspots on the planar surface, the modified Au NTs showed much better SERS performance than initial Au NTs. By combination of the rough-surfaced Au NTs with MXene, the Ti3C2T x /Au NT hybrids exhibited much better SERS performance than initial Au NTs and Au NTs with a rough surface. The detection limit is down to 10-12 M, and the analytical enhancement factors reach 3.6 × 109 (at 1174 cm-1) on detecting crystal violet excited at 785 nm. This is because the strong plasmon coupling between the in-plane resonance of Au NTs and transversal plasmon resonance of Ti3C2T x MXene around 785 nm can generate an intense interfacial electromagnetic field for amplifying SERS signals. Additionally, the efficient charge transfer between Au NTs, MXene, and molecules also plays an important role in enhancing the SERS performance. This work presents a new insight to develop high-performance SERS substrates based on plasmon.

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